Details of the Drug Combination

General Information of Drug Combination (ID: DCBPD5V)

• Drug Combination Name: Buspirone + Maprotiline
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Buspirone (DMBS632): Small molecular drug
  Maprotiline (DMPWB7T): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 4.67
  Bliss Independence Score: 4.67
  Loewe Additivity Score: 5.67
  LHighest Single Agent (HSA) Score: 5.67

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Buspirone

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Approved	[2]

Buspirone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Agonist	[5]

Buspirone Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[8]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Metabolism	[9]

Buspirone Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases Oxidation	[7]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Oxidation	[7]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[10]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[11]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[11]

Indication(s) of Maprotiline

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[3]
Major depressive disorder	6A70.3	Approved	[4]
Mixed anxiety and depressive disorder	N.A.	Investigative	[3]

Maprotiline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[12]

Maprotiline Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[13]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[13]

Maprotiline Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[14]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[15]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 36).
• [3] Maprotiline FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [6] Effects of cytochrome P450 (CYP) 3A4 inhibitors on the anxiolytic action of tandospirone in rat contextual conditioned fear. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):926-31.
• [7] Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes. Drug Metab Dispos. 2005 Apr;33(4):500-7.
• [8] Drug Interactions Flockhart Table
• [9] The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
• [10] Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
• [11] Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment. Psychoneuroendocrinology. 2010 May;35(4):481-9. doi: 10.1016/j.psyneuen.2009.08.012. Epub 2009 Sep 16.
• [12] Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.
• [13] Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9.
• [14] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [15] The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma. Int J Cancer. 2011 Apr 1;128(7):1712-23. doi: 10.1002/ijc.25477. Epub 2010 May 25.